Role of p53 and ATM in photodynamic therapy-induced apoptosis

Background and Objectives: Photodynamic therapy (PDT) induces cell death through a laser light-activated photosensitizer and is a treatment option for tumors resistant to radio- and chemo-therapy. Study Design/Materials and Methods: We investigated whether m-THPC-PDT induces cell death by necrosis and/or apoptosis, and whether these responses are modulated by p53 and/or ATM, two cancer-associated genes. Sensitivity of atm(+/+)p53(+/+), atm(+/+)p53(-/-), and atm(-/-)p53(-/-) mouse embryonic fibroblasts to m-THPC-PDT performed at a wavelength of 652 nm was determined by the MTT assay, trypan blue-exclusion, and the TUNEL and caspase3-cleavage apoptosis assays. c-Abl protein level was determined by immunoblotting. Results: m-THPC-PDT rapidly induced cell death in a substantial fraction of cells by p53- and Ataxia telangiectasia mutated (ATM)-independent non-apoptotic processes. However, in the subset of apoptotic cells, apoptosis was reduced by loss of p53 and was even more reduced by the additional loss of ATM. Apoptosis correlated inversely with c-Abl level. Conclusions: p53 and ATM are not required for necrosis, but may be required for PDT-mediated apoptosis. (C) 2003 Wiley-Liss, Inc.